The aim of this meta-analysis was to assess the effectiveness of glutamine to treat severe mucositis induced by radiation therapy in patients with head and neck cancer. We undertook electronic searches of PubMed (1990 to January 2015), Embase (1990 to January 2015), and the Cochrane Library (2013, Issue 2) to identify relevant studies. We included randomized controlled trials of glutamine to alleviate oral mucositis (OM) in patients with head and neck cancer who received radiotherapy. Information regarding methods, patients, results, and risk of bias was independently extracted by two authors. Statistical analyses were conducted to calculate the odds ratio and 95% confidence intervals (95%CIs) using fixed-effect models. We identified five clinical studies that included 234 patients with head and neck cancer. All studies were assessed as being at low risk of bias in most items of six domains. In this meta-analysis, glutamine treatment showed a statistically significant benefit with respect to reducing the risk and severity of OM induced by radiotherapy compared to either placebo or no treatment (risk ratio 0.17, 95%CI 0.06-0.47). Overall, glutamine significantly reduces the risk and severity of OM during radiotherapy or chemotherapy. Further prospective and large trials are required to support the findings.